Novel p-aminobenzoates

ABSTRACT

NOVEL N-SUBSTITUTED ANILINES OF FORMULA I USEFUL FOR THE CONTROL OF INSECTS.

UnitedStates Patent 3,803,211 NOVEL p-AMINOBENZOATES Ladislav Dolejs, 56Letohradska; Pavel Beran, 7 Nat.

Obrany; Jitka Kahovcova, 3 ul. P. Rezka; Zuzana Machova, 7 Mezibranska;Karel Slama, 674 Na cervenem vrchu; and Frantisek Sam, 9 Korejska, all

of Prague, Czechoslovakia No Drawing. Filed Dec. 14, 1970, Ser. No.98,093 Claims priority, application Czechoslovakia, Dec. 23,

1969, 8,513/69 Int. Cl. C07c 101/60 US. Cl. 260-471 R v 9 ClaimsABSTRACT OF THE DISCLOSURE Novel N-substituted anilines of Formula Iuseful for the control of insects.

This invention relates to a process of preparing novel compounds for thecontrol of insects and to the novel compounds of Formula I:

R: i G

N X R1 (1) wherein,

X is

0 II II 0-0 R3 or --CR= in which R is hydrogen, lower alkyl, aryl oraralkyl;

Y is hydrogen, or together with X, forms a methylenedioxy bridge; R isone of the groups A, B or C:

3: i 11 -6-CEli-(CH2)rJl-CH-(CHzh-{P-CH-CHr- Z l l in which each of R,R, R and R is hydrogen or lower alkyl; Z is hydrogen and Z is hydrogen,or together with Z, a carbon-carbon bond; Z is hydrogen and Z ishydrogen, or together with Z a carbon-carbon bond; Z is hydrogen and Zis hydrogen, or together with Z 21 carbon-carbon bond;

R is hydrogen, methyl, ethyl, propyl, n-butyl or one of the groups A, Bor C;

m is the positive integer one or two; and

n is the positive integer two or three.

The term aryl, as used herein, refers to an aryl group of six to twelvecarbon atoms, such as phenyl, naphthyl and methylphenyl.

The term lower alkyl, as used herein, refers to an Patented Apr. 9, 1974to the immature insect, namelyduring the embryo, larvae or pupae stagein view of their ability to inhibit metamorphosis and otherwise causeabnormal development. These compounds are effective control agents forHemipteran, such as Lygaeidae, Miridae and Pyrrhocoridae; Coleopteran,such as Tenebrionidae; Lepidoptern, such as Pyralidae, Noctiidae andGelechiidae; Dipteran, such as mosquitoes; Orthoptera such as roaches;and Homoptera, such as aphids. The compounds can be applied at lowdosage leveles ofthe order of 0.001 ,ug. to 25 g, per insect. Suitablecarrier substances include liquid or solid carriers, such as water,mineral or vegetable oils, talc, silica and natural or synthetic resin.The control of insects in accordance with the present invention isaccomplished by spraying, dusting or exposing the .insects t0v the vaporof .the novel compounds. Generally,

a concentration of less than 50% of the active compound is employed. Theformulation can include insect attractants, emulsifying agents andwetting agents to assist in the application and efiiciency of the activeingredient.

In the description following, each of X, Y, R to R Z -to Z m and n areas defined above.

The compounds of Formula I are prepared, preferably in an organicsolvent inert to the reaction, by reacting an aniline of Formula II:

1 Y H\ I with an alkylating agent M1 in which Z is bromo or chloro.

The halide R -Z in which R is the group B or C can be prepared from thecorresponding C-1 alcohol which is obtained by reduction of an acid orester of the formula:

in which R is hydrogen or lower alkyl, using lithium aluminum hydride,or the like. The overall synthesis can be outlined as follows:

In the practice of the above process, a dialkyl ketone of Formula H1 isreacted with a Wittig reagent of Formula HI is phenyl):

L J to form the ethylene ketal of a compound of Formula IV which ishydrolyzed by treatment with acid to the ketone (IV). The ketone (IV) isthen reacted with the carbanion of dialkyl carbalkoxyphosphonate toyield the cap-unsaturated ester (V; m is zero and R is lower alkyl) orwith fl-carboxyethyltriphenylphosphonium chloride in the presence ofbase to yield fl,'y-unsaturated acid (V; m is one 3 and R is hydrogen).Suitable conditions are described by -H. S. Corey et al., J. Am. Chem.Soc. 86, 1884- 1885 (1964), the disclosure of which is incorporated byreference. The acid or ester (V) is then reduced by conventionaltechniques using lithium aluminum hydride or like reducing agent toyield the primary alcohol (VI) which is converted to the C-1 bromide orchloride using phosphorus trichloride, phosphorus tribromide, phosphoruspentachloride, phosphorus pentabromide, or the like. The halidealkylating agents can be prepared also using the synthesis of Bowers,Science 164, 323-325 (1969) which is incorporated by reference. Thecompounds of Formula IV are prepared by reduction of the ketone (1V)using sodium borohydride, lithium aluminum hydride, or the like, and theconversion of the secondary alcohol into the bromide or chloride usingphosphorus tribromide or phosphorus trichloride. Hydrogenation usingpalladium or other catalyst yields the saturated and mono-saturatedalkylating agents. I

The following examples are provided to illustrate the practice of thepresent invention and the preparation of the novel compounds.Temperature is given in degrees centigrade.

EXAMPLE 1 3,4-methylenedioxyaniline (2 g.) is dissolved indimethylformamide ml.) and the solution is treated with geranyl bromide(4 g.) and anhydrous potassium carbonate (2.6 g.). The reaction mixtureis heated at 70 C. for 12 hours, diluted with water and extracted withether. The ethereal layer is dried over anhydrous sodium sulfate,evaporated and the residue fractionated under diminished pressure toyield N-geranyl 3,4-methylenedioxyaniline.

By use of the above procedure, 3,4-methylenedioxyaniline is alkylatedusing 3,7-dimethyloct-6-enyl bromide, 1,5-dimethylhex-4-enyl bromide,3,7 dimethylnona-2,6- dienyl bromide, 3-ethyl-7-methylnona-2,6-dienylbromide and 4,8-dimethylnona-3,7-dienyl bromide to yield the anilinesunder Column 1:

N-3,7-dimethyloct-6enyl 3,4-methylenedioxyaniline,

N-1,5-dimethylhex-4-enyl 3,4-methylenedioxyaniline,

N-3,7-dimethylnona-2,6-dienyl 3,4-methylenedioxyaniline,

N-3-ethyl-7-methylnona-2,6-dienyl 3,4-methylenedioxyaniline,

N-4,8-dimethylnona-3,7-dienyl 3,4-methylenedioxyaniline.

EXAMPLE 2 A 50% suspension of sodium hydride in mineral oil (0.5 g.) ismixed under nitrogen with purified dioxane (15 ml.) and ethylp-aminobenzoate (1.65 g.) in dioxane (10 ml.) is added. The wholemixture is refluxed for two hours, treated with a solution of geranylbromide (2.45 g.) in dioxane (15 ml.) and the reflux continued undernitrogen for another two and one-half hours. The reaction mixture iscooled, filtered and the filtrate evaporated under diminished pressureto remove dioxane. The residue is shaken with a mixture of water andether, the ethereal layer is washed with 5% aqueous hydrochloric acid,dried over anhydrous sodium sulfate and evaporated. The residue ispurified by column chromatography on silica gel to yield ethylN-geranyl-p-aminobenzoate.

Each of the bromides listed in Example 1 is used as the alkylating agentin the process of Example 2 to yield the ethyl p-aminobenzoates underColumn 11:

ethyl N-3,7-dimethyloct-S-enyl-paminobenzoate,

ethyl N-l,5-dimethylhex-4-enyl-paminobenzoate,

ethyl N-3,7-dimethylnona-2,6-dienyl-p-aminobenzoate, ethylN-3-ethyl-7-methylnona-2,6-dienyl-p-aminobenzoate, ethyl N-4,8-dimethylnona-3,7-dienyl-p-aminobenzoate.

, 4 EXAMPLE 3 The process of Example 2 is repeated using methylp-aminobenzoate to yield methyl N-geranyl-p-aminobenzoate and methylN-3,7-dimethyloct-6-enyl-p-aminobenzoate. Other methyl N-substitutedp-aminobenzoates are prepared using an alkylating agent of the formula RZ following the procedure of Example 2. 7

EXAMPLE 4- Methyl p-aminophenylketone is alkylated using geranyl bromideand citronellyl bromide followingthe procedure of Example 2 to yieldmethyl N-geranyl p-aminophenylketone and methyl N-citronellylp-aminophenylketone. Similarly, using farnesyl bromide as the alkylatingagent, there is obtained methyl N-farnesyl p-aminophenylketone.

Ethyl p-aminophenylketone. is alkylated using the procedure of Example 2to yield the corresponding compounds of Formula 1.

Each of the methyl N-geranyl p-aminobenzoate,- methyl N-citronellylp-aminobenzoate and N-geranyl 3,4-methylenedioxy-aniline were testedtopically on 5th instar larvae of Triatoma infestans and found to havean ID of 0.5, 0.1 and 01 micrograms. The method of testing is describedby Slain-la, Romanuk and Sorum, The Biological Bulletin 136, 91-95(1969).

What is claimed is:

1. A compound selected from those of the following formula:

in which each of R, R R aind R is hydrogen or lower alkyl; Z is hydrogenand Z is hydrogen or together with Z, a carbon-carbon bond; Z ishydrogen and Z is hydrogen, or together with Z a carbon-carbon bond; Zis hydrogen and Z is hydrogen, or together with Z a carboncarbon bond;

R is hydrogen, methyl, ethyl, propyl, n-butyl or one of the groups A, Bor C; m is the positive integer one or two; and n is the positiveinteger two or three.

2. A compound according to claim 1 wherein R is the group:

R 4 R -b-oH- orn)..-b-oH- crr,

3. A compound according to claim 2 wherein m is one A and n is two.

4. A compound according to claim 3 wherein R is methyl or ethyl; each ofR R and R is methyl or ethyl and R is hyd ogen.

wherein X is in which each of R, R and R is hydrogen or lower alkyl;

Z is hydrogen and Z is hydrogen, or together with Z a carbon-carbonbond;

Z is hydrogen and Z is hydrogen, or together with Z a carbon-carbonbond;

R is hydrogen, methyl, ethyl, propyl, n-butyl or R m is the positiveinteger one or two; and

n is the positive integer two or three.

9. A compound according to claim 1 which is ethyl-N-geranyl-p-aminobenzoate.

References Cited UNITED STATES PATENTS 3,671,558 6/1972 Siddall et al.260-471 R LORRAINE A. WEINBERGER, Primary Examiner L. A. THAXTQN,Assistant Examiner US. Cl. X.R.

